Enhanced RAD21 cohesin expression confers poor prognosis in BRCA2 and BRCAX, but not BRCA1 familial breast cancers

Yan, Max, Xu, Huiling, Waddell, Nic, Shield-Artin, Kristy, Haviv, Izhak, McKay, Michael J., Fox, Stephen B. and KConFab Authors (2012) Enhanced RAD21 cohesin expression confers poor prognosis in BRCA2 and BRCAX, but not BRCA1 familial breast cancers. Breast Cancer Research, 14 2: R69.1-R69.11. doi:10.1186/bcr3176


Author Yan, Max
Xu, Huiling
Waddell, Nic
Shield-Artin, Kristy
Haviv, Izhak
McKay, Michael J.
Fox, Stephen B.
KConFab Authors
Total Author Count Override 62
Title Enhanced RAD21 cohesin expression confers poor prognosis in BRCA2 and BRCAX, but not BRCA1 familial breast cancers
Journal name Breast Cancer Research   Check publisher's open access policy
ISSN 1465-542X
1465-5411
Publication date 2012
Sub-type Article (original research)
DOI 10.1186/bcr3176
Open Access Status DOI
Volume 14
Issue 2
Start page R69.1
End page R69.11
Total pages 11
Place of publication London, United Kingdom
Publisher Current Medicine Group
Collection year 2013
Language eng
Formatted abstract
Introduction: The RAD21 gene encodes a key component of the cohesin complex, which is essential for chromosome segregation, and together with BRCA1 and BRCA2, for high-fidelity DNA repair by homologous recombination. Although its expression correlates with early relapse and treatment resistance in sporadic breast cancers, it is unclear whether familial breast cancers behave in a similar manner.

Methods: We performed an immunohistochemical analysis of RAD21 expression in a cohort of 94 familial breast cancers (28 BRCA1, 27 BRCA2, and 39 BRCAX) and correlated these data with genotype and clinicopathologic parameters, including survival. In these cancers, we also correlated RAD21 expression with genomic expression profiling and gene copy-number changes and miRNAs predicted to target RAD21.

Results: No significant differences in nuclear RAD21 expression were observed between BRCA1 (12 (43%) of 28), BRCA2 (12 (44%) of 27), and BRCAX cancers (12 (33%) of 39 (p = 0.598). No correlation was found between RAD21 expression and grade, size, or lymph node, ER, or HER2 status (all P > 0.05). As for sporadic breast cancers, RAD21 expression correlated with shorter survival in grade 3 (P = 0.009) and but not in grade 1 (P = 0.065) or 2 cancers (P = 0.090). Expression of RAD21 correlated with poorer survival in patients treated with chemotherapy (P = 0.036) but not with hormonal therapy (P = 0.881). RAD21 expression correlated with shorter survival in BRCA2 (P = 0.006) and BRCAX (P = 0.008), but not BRCA1 cancers (P = 0.713). Changes in RAD21 mRNA were reflected by genomic changes in DNA copy number (P < 0.001) and by RAD21 protein expression, as assessed with immunohistochemistry (P = 0.047). High RAD21 expression was associated with genomic instability, as assessed by the total number of base pairs affected by genomic change (P = 0.048). Of 15 miRNAs predicted to target RAD21, mir-299-5p inversely correlated with RAD21 expression (P = 0.002).

Conclusions: Potential use of RAD21 as a predictive and prognostic marker in familial breast cancers is hence feasible and may therefore take into account the patient's BRCA1/2 mutation status.
Keyword Gene-expression
Tissue microarray
Dna-damage
Mutations
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number R69

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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